Project Summary The 2020 (Systems Neuroscience and Genetic Approaches to Study Sleep Regulation and Function) will be the fourth Sleep GRC. In this meeting we will cover topics that have not been included in past meetings. Past meetings have discussed how modulating sleep regulatory neurons using optogenetics or chemogenetics impacts sleep time. However, there is a growing awareness that seemingly homogenous neurons are, in fact, much more heterogeneous than previously believed. Identifying and gaining genetic access to neurons with unique properties so that they can be manipulated and monitored will be essential for fully understanding sleep regulation and function. Thus this meeting will begin by discussing new strategies for defining neuronal identity in diverse brain regions important for sleep. Identifying additional sleep regulatory components injects an added layer of complexity that makes it difficult to fully understand sleep regulation. As such, theoretical approaches for modeling how these new sleep-regulatory components might interact will be discussed. Importantly, the ability to identify and monitor specific neuronal subtypes is relevant to the future success of many topics presented throughout the meeting. Chief amongst these is a session devoted to understanding how metabolic factors impact the sleep-wake cycle; a long standing goal of sleep research. Although past meeting have included discussion on how sleep-specific electrophysiological signals (e.g. sleep spindles) modulate discrete brain regions, this meeting will examine how sleep impacts global brain dynamics in c elegans, Drosophila and mice and try and identify common, and evolutionarily conserved, regulatory principles. Given that sleep is a global phenomenon that impacts the entire brain, the 2020 Sleep GRC will extend the conversation of sleep function beyond synapses and memory. One session will discuss the impact of sleep during development on brain functioning and an additional session will examine the role of sleep in regulating of positive and negative emotions. Importantly these sessions will include the most recent studies using molecular-genetic approaches for identify underlying circuitry and genes in animals as well as genetic and imaging studies in humans. A past meeting has covered the relationship between sleep and Alzheimer?s disease but new advances in the field using human transcriptomics and imaging techniques are shedding new light on this topic and will be discussed in 2020. Finally, since genes alter behavior by impacting specific neuronal circuits, we will conclude the meeting by discussing recent developments in identifying new genes that modulate sleep in mice and humans.